Binding to cell surface receptors must be the initial event in virus-cell recognition regardless of the ultimate mechanism of viral infection. We have developed an in vitro assay which quantifies Rous sarcoma virus (RSV) absorption to chicken fibroblast plasma membranes. The membrane receptor for Rous sarcoma virus is protease labile, and membranes from genetically resistant chick embryo fibroblasts contain receptor activity. The receptor, which has been solubilized by two independent techniques, is alkali labile, heat stable, will bind directly to RSV, and inhibits RSV induced cell transformation. Our present program is directed toward purification and chemical identification of the receptor through: (1) classical biochemical fractionation of the solubilized receptors; (2) continued manipulation of the cell surface in an attempt to indirectly ascertain structural information. The density of the receptor will be quantified on permissive and resistant chick cells, and the receptor from these latter cells will be compared to that purified from susceptible cells. Experiments are planned to show that, following initial absorption, receptors bind to virus in a multivalent fashion forming a cluster on the membrane surface. Companion studies will be directed toward blocking receptor aggregation by manipulating the membrane phospholipid composition in cells in culture, and utilizing cross-linking agents to inhibit receptor mobility. Finally, membrane models will be constructed incorporating the purified receptor in order to study viral binding so that the role of the receptor in viral penetration can be further clarified.